Transcript Outbreak Investigation - Department of Health Home

Outbreak Investigation:
Discussion Group
Ebbing Lautenbach, MD, MPH
Assistant Professor of Medicine and
Epidemiology
Senior Scholar, CCEB
Associate Hospital Epidemiologist, HUP
Initial Call
• Late June, 1997: Calls from 4 MDs
reporting 6 patients with bloody diarrhea
and E. coli O157:H7 infection
Initial Call
• Late June, 1997: Calls from 4 MDs
reporting 6 patients with bloody diarrhea
and E. coli O157:H7 infection
• 1 day later: Call from Michigan Department
of Community Health (MDCH)
• Increase in laboratory reports
of E. coli O157:H7
– June 1997 = 52
First….
Steps in Outbreak Investigation
1. Verify the Diagnosis
1. Verify the Diagnosis
• Escherichia coli O157:H7 first identified as a
human pathogen in 1982 in the US
• Sporadic infections and outbreaks since reported
from many parts of the world (e.g., N. America,
Western Europe, Australia, Asia, and Africa)
• Cattle are the primary reservoir for E. coli
O157:H7
• Implicated foods are typically those derived from
cattle (e.g., beef, hamburger, raw milk);
• Infection has also been transmitted through
contact with infected persons, contaminated
water, and other contaminated food products.
1. Verify the Diagnosis
• Infection with E. coli O157:H7 is diagnosed
by detecting the bacterium in the stool.
• Only recently has E. coli O157:H7 infection
become nationally notifiable in many parts
of the U.S.
Steps in Outbreak Investigation
1. Verify the Diagnosis
Steps in Outbreak Investigation
1. Verify the diagnosis
2. Confirm the outbreak
Trends in MDCH E. Coli O157 Cases
60
50
# Cases
40
30
20
10
0
J
J
A
S
1996
O N
D
J
F M A M
1997
J
What could account for the
increase in cases?
What could account for the
increase in cases?
Real increase
• Increase in population size
• Changes in population
characteristics
• Random variation
• Outbreak
Artificial increase
• Increased cx of stools
• New testing protocol
• Contamination of cxs
• Changes in reporting
procedures
Initial Investigation
• No substantial changes in population size
• No appreciable changes in the population
characteristics
• No laboratory based changes
– Surveillance / testing
– Reporting protocol
Initial Investigation
• Any other way to see if there is a
relationship between these E. coli isolates?
Molecular Epidemiology
• DNA fingerprinting
• Pulsed Field Gel Electrophoresis (PFGE)
most common in outbreak investigations
• A cluster of isolates with the same PFGE
pattern suggests they arose from the same
parent (same source)
• Still need an epidemiologic investigation
PFGE pattern of E. coli Isolates
Molecular Epidemiology of E.
coli Isolates
• 17 of the first 19 E. coli O157:H7 isolates
from June-July were indistinguishable.
• They did not match any fingerprints from a
convenience sample of isolates from
patients with E. coli O157:H7 infection
before May.
Steps in Outbreak Investigation
1. Verify the diagnosis
2. Confirm the outbreak
Steps in Outbreak Investigation
1. Verify the diagnosis
2. Confirm the outbreak
3. Case definition
3. Develop a Case Definition
• Incubation period for E. coli O157:H7 ranges
from 3-8 days with a median of 3-4 days.
• The infection often causes severe bloody diarrhea
and abdominal cramps, but can also cause a nonbloody diarrhea or result in no symptoms.
• In some persons, particularly children
under 5 years of age and the elderly,
infection can be complicated by
hemolytic uremic syndrome
(occurs in about 2-7% of infections)
Case Definition?
Case Definition
• Outbreak investigation definition:
1. diarrhea (>3 loose bowel movements a day)
and/or abdominal cramps
2. resident of Michigan
3. onset of symptoms between June 15 and July 15
4. stool culture yielding E. coli O157:H7 with the
outbreak strain PFGE pattern.
• Advantages? Disadvantages?
Case Definition
• Advantages:
– Lab confirmation increases specificity of case definition
• Reduces misclassification; maximizes power to detect source.
• Disadvantages:
– Lab confirmation
• Excludes patients who did’nt see MD, were not cxd, or cxd without PFGE.
• Decreases the sensitivity of the case definition
• Possibly leads to a misrepresentation of case characteristics.
– Limiting cases to Michigan residents
• excludes visitors who became infected; inhibits recognition of extension
of outbreak into other states.
– Dates reasonable?
• Need more information
• Could limit the number of secondary cases included in the study that could
interfere with identification of the initial source of the outbreak.
Steps in Outbreak Investigation
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Steps in Outbreak Investigation
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive Epidemiology
Characterization of Cases
Of the initial 38 persons who met the case definition, 26 (68%)
were female with a median age of 31 years.
Table 1. Age group and gender distribution for persons with E. coli O157:H7
infection (with PFGE pattern), Michigan, June 15 - July 15, 1997. (N=38)
Age group
(years)
Gender
TOTAL
Male
Female
0-9
2 (17%)*
2 (8%)
4 (11%)
10-19
2 (17%)
3 (12%)
5 (13%)
20-39
3 (25%)
9 (35%)
12 (32%)
40-59
2 (17%)
8 (31%)
10 (26%)
60+
3 (25%)
4 (15%)
7 (18%)
12 (101%)
26 (101%)
38 (100%)
TOTAL
* percentages refer to column totals.
Age group
(years)
MI Cases
TOTAL
Male
Female
0-9
2 (17%)*
2 (8%)
4 (11%)
10-19
2 (17%)
3 (12%)
5 (13%)
20-39
3 (25%)
9 (35%)
12 (32%)
40-59
2 (17%)
8 (31%)
10 (26%)
60+
3 (25%)
4 (15%)
7 (18%)
12 (101%)
26 (101%)
38 (100%)
TOTAL
.
Gender
Gender
APPENDIX 1
TOTAL
Age group
(years)
FoodNet
Data
Male
Female
0-<1
5 (3%)
5 (3%)
10 (3%)
1-9
77 (48%)
77 (43%)
154 (45%)
10-19
36 (22%)
18 (10%)
54 (16%)
20-29
10 (6%)
20 (11%)
30 (9%)
30-39
6 (4%)
12 (7%)
18 (5%)
40-49
7 (4%)
5 (3%)
12 (4%)
50-59
7 (4%)
17 (10%)
24 (7%)
60+
14 (9%)
24 (13%)
38 (11%)
162 (100%)
178 (100%)
340 (100%)
TOTAL
Michigan counties
The 38 cases of E.
coli O157:H7
infection meeting
the investigation
case definition
were reported
from 10 counties
in the lower
peninsula of
Michigan.
Epidemic Curve
Figure 3. Date of illness onset for persons with E. coli O157:H7 infection
and the outbreak PFGE pattern, MI, June 15 - July 15, 1997. (N=38)
Epidemic Curves
• How to set it up
• What it tells you
– Mode of transmission
• Propagated
• Common source
– Timing of exposure
– Course of exposure
Epidemic Curves
Propagated source: single exposure, no secondary cases
(e.g., measles)
8
7
6
Cases
5
4
3
2
1
0
1
2
3
4
5
6
7
Week
8
9
10
11
12
Epidemic Curves
Propagated source: secondary and tertiary cases (e.g.,
hepatitis A)
10
9
8
Cases
7
6
5
4
3
2
1
0
1
2
3
4
5
6
7
Week
8
9
10
11
12
Epidemic Curves
Common source: point exposure (e.g., salmonella)
8
7
6
Cases
5
4
3
2
1
0
1
2
3
4
5
6
7
Days
8
9
10
11
12
Epidemic Curves
Common source: Intermittent exposure (e.g.,
contaminated blood product)
8
7
6
Cases
5
4
3
2
1
0
1
2
3
4
5
6
7
Days
8
9
10
11
12
Epidemic Curve
Figure 3. Date of illness onset for persons with E. coli O157:H7 infection
and the outbreak PFGE pattern, MI, June 15 - July 15, 1997. (N=38)
Steps in Outbreak Investigation
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Steps in Outbreak Investigation
•
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive Epidemiology
Develop a hypothesis
Developing a Hypothesis
Ask questions!!
But of whom….
And when...
Determining the Probable Period
of Exposure
• Mean/Median incubation period
• Minimum/maximum incubation period
Estimating date of exposure
Peak
One incubation period
10
Probable time of exposure
9
8
7
Cases
Rubella = 18 days
6
5
4
3
2
1
0
1
3
5
7
9
11
13
15
Days
17
19
21
23
25
27
29
Estimating date of exposure
Maximum incubation
Probable time of exposure
21 days
10
9
8
Cases
7
6
5
4
3
Minimum incubation
2
14 days
1
0
1
3
5
7
9
11
13
15
Days
17
19
21
23
25
27
29
E. Coli Epidemic Curve
Figure 3. Average incubation period = 4 days ( range 3-8 days)
Focus of Questions
Focus of Questions
• demographic information
• clinical details of the illness with date of onset,
duration, and severity of symptoms
– visits to health care providers or hospitals, and laboratory
results
• a complete food history in the last 7 days
• water exposure in the last 7 days (e.g., drinking water,
exposure to recreational waters)
• exposure to other ill persons in the last 7 days
• exposure to children in day care in the last 7 days
• exposure to a farm or farm animals in the last 7 days
• travel outside the immediate area in the last 7 days
Interview Results
Variable
Female
Med Age
Rec water exposure
Other Ill person
Day care
Farm
Fair
Travel
Hamburger
Meat
Milk
Alfalfa sprouts
Lettuce
Cases (n=38)
26 (68%)
31
13 (34%)
6 (16%)
18 (47%)
2 (5%)
18 (47%)
9 (24%)
25 (66%)
22 (58%)
32 (84%)
19 (50%)
24 (63%)
Findings Thus Far
• Cases are spread over 10 counties
– No uniform attendance at any common event
– Onset of symptoms among known cases extends over
approximately one month.
• The median age of patients is 31 years (range 276); 68% of cases are among females.
• Factors present in over 50% of cases:
– Female, milk, hamburger, lettuce, alfalfa sprouts
– Role of fair attendance, water exposure?
Hypothesis?
Hypothesis of Investigators
• Lettuce and/or alfalfa sprout consumption is
associated with E. coli infection
Steps in Outbreak Investigation
•
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Develop a hypothesis
Steps in Outbreak Investigation
•
•
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Develop a hypothesis
Test the hypothesis
Pick a Control Group
Controls Selected
• 2 controls selected for every case
• Matched to the case by:
– Age group
• (0-<2 years, 2-<5 years, 5-<12 years, 12-<18
years, 18-<60 years, and 60+ years)
– Sex
Methods to Identify Controls
• Random digit dailing
• Neighborhood controls
• Other patients of same physician
Selection of Controls
• The investigators identified controls for the study
using random digit dialing.
• Exposure information among cases was collected
for the 7 days before onset of illness.
• For controls, exposure information was collected
for the 7 days before the interview and for the 7
days before the onset of illness in the matching
case.
• Twenty-seven case-control sets were interviewed;
the remaining case-patients could not be reached.
Interview Results
Variable
Female
Med Age
Rec water exposure
Other Ill person
Day care
Farm
Fair
Travel
Hamburger
Meat
Milk
Alfalfa sprouts
Lettuce
Cases (n=27)
18 (67%)
31
9 (33%)
6 (22%)
16 (59%)
2 (7%)
12 (44%)
8 (30%)
17 (63%)
14 (52%)
21 (78%)
15 (56%)
18 (67%)
Controls (n=54)
36 (67%)
31
21 (39%)
9 (17%)
33 (61%)
2 (4%)
24 (44%)
13 (24%)
36 (67%)
26 (48%)
44 (81%)
4 (7%)
34 (62%)
E. coli and Alfalfa Sprouts?
Variable
Cases
15 (56%)
Controls
4 (7%)
OR (95%CI)
25 (4-528)
No other food item was significantly associated with
illness.
Steps in Outbreak Investigation
•
•
•
•
•
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Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Develop a hypothesis
Test the hypothesis
Steps in Outbreak Investigation
•
•
•
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Develop a hypothesis
Test the hypothesis
Refine hypothesis / Execute additional studies
Refine Hypothesis/Additional Studies
• What control measures might you consider at this
point?
• What further studies might you do?
Additional Studies
• Culture implicated sprouts
• Traceback study
– distributor, processor, and producer; examination of the
chain of production of the sprouts from the farm to the
table
• Applied research on E. coli
– research on alfalfa sprouts and survival/growth of E.
coli O157:H7 (e.g., the ability of E. coli to survive and
grow on alfalfa seeds/sprouts at each step of the
production process).
Traceback Studies
• Often necessary to identify sources of contamination
and quickly limit a public health threat by removing
these sources.
• Ascertain the distribution and production chain for a
food product to facilitate effective recall.
• Clarify the point or points at which the implicated
food was likely to have become contaminated
Traceback Results
Follow up
• The implicated seed lot was a blend of 5 lots from fields of
four farmers and was harvested between 1994 and 1996.
The seed processor and the farmers were located in Idaho.
• Inspection of the alfalfa fields revealed three possible
sources of contamination: cattle manure, irrigation water,
and deer feces.
– Manure is not normally applied to alfalfa fields in Idaho
– Cattle feed lots were common in this area and the alfalfa fields of
one farmer were adjacent to a feed lot.
– Manure may have leaked or been illegally dumped onto the alfalfa
fields or run-off water from neighboring fields, contaminated by
manure, may have been used to irrigate the alfalfa fields.
– In addition, three of four farmers occasionally saw deer in their
fields and one field was situated next to a wildlife refuge.
Steps in Outbreak Investigation
•
•
•
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Develop a hypothesis
Test the hypothesis
Refine hypothesis / Execute additional studies
Steps in Outbreak Investigation
•
•
•
•
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Develop a hypothesis
Test the hypothesis
Refine hypothesis / Execute additional studies
Implement control and prevention measures
What interventions are Needed?
• 2 issues:
– 1) the immediate problem with this
implicated lot of seed
– 2) the larger issue of seed sprouts as
vehicles for pathogenic
What interventions are Needed?
• Implicated seed lot
•
all remaining seeds and alfalfa sprouts from the implicated
lot should be removed from the market.
– Persons who have purchased sprouts from the implicated lot
should be instructed to destroy any remaining sprouts or return
them to the store at which they were purchased.
• The producers of these particular seeds should be informed
of the need to protect alfalfa and other seeds used in
sprouting from contamination during growing, harvesting,
and packing.
• Specific sources of contamination should be identified and
eliminated from these growing sites.
What interventions are Needed?
• Seed sprouts are high risk vehicle for foodborne diseases
• Continue applied research to find ways to successfully
decontaminate the seeds/sprouts.
• Educate sprout growers on appropriate growing conditions and
handling of sprouts to limit contamination.
• Educate the public about the riskiness of sprouts
– Persons at high risk for complications of infection (e.g., children <5 years of
age, immunocompromised individuals, and the elderly) avoid sprouts.
• Require sprout producers to label sprouts as risky foods
• Remove sprouts from the market for human consumption until
their safety can be assured.
Steps in Outbreak Investigation
•
•
•
•
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Develop a hypothesis
Test the hypothesis
Refine hypothesis / Execute additional studies
Implement control and prevention measures
Steps in Outbreak Investigation
•
•
•
•
•
•
•
•
•
Verify the diagnosis
Confirm the outbreak
Case definition
Descriptive epidemiology
Develop a hypothesis
Test the hypothesis
Refine hypothesis / Execute additional studies
Implement control and prevention measures
Communicate findings
Communicate Findings
• The implicated seed lot was not distributed to any other
sprouting companies. The remaining 6,000 lbs. of seed was
immediately removed from the marketplace.
• The Idaho Division of Food and Drugs held meetings at
which public health officials explained to seed growers the
need to protect alfalfa and other seeds used in sprouting from
contamination during growing, harvesting, and packing.
• Public television and radio announcements about the risk of
contaminated sprouting seeds, recommending persons at high
risk for complications from E. coli O157:H7 not eat sprouts.
• The Center for Food Safety and Quality Enhancement began
working with the sprout industry to identify ways to make
sprouts safer for human consumption.
Conclusions
• Importance of applying the multi-step approach in
outbreak investigation
• Utility of new subtyping methods such as PFGE
• Importance of disease reporting
• Flexibility of hypothesis generation
– New vehicle for the transmission of E. coli O157:H7
• Increasing geographic dissemination of outbreaks